The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

Bringing antiretroviral drugs to children

“
test the safety and efficacy of this new formulation in young children

”

Southern Africa has some of the world’s highest burdens of poverty-related infectious diseases, particularly HIV/AIDS and TB. Co-infections are common and drug resistance is a growing threat.

On the other hand, the sub-region has a number of internationally recognised research centres, and generates a significant proportion of sub-Saharan Africa’s research outputs. These centres of excellence provide opportunities to act as foci to build capacity in less well-developed institutions.

The challenge

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The project

TESA was established in 2009 with EDCTP funding, initially with nine institutions from six countries. Its key aim was to develop and promote collaborations to support capacity building and training in participating institutions. During phase I funding, more than 80 students and clinical research staff received short-term training, 30 courses were organised, and 11 master’s, eight PhD and one postdoctoral fellowship were awarded. 

In addition, multiple laboratory sites were upgraded, baseline epidemiological studies carried out and consistent standard operating procedures were introduced.

In follow-up TESA II funding, the network expanded to include 15 institutions from eight Southern African countries, one East African country and four European countries. Four institutions were selected to act as reference centres, one for each specific disease area (HIV/AIDS, TB and malaria), while one institution acts as the reference data management centre. The reference centres provide support to other sites in the network, as well as conducting training and capacity development in their respective areas.

During TESA II, the network has supported the long-term training of a further eight master’s students, four PhD students and a postdoctoral researcher. Short-term training and exchange visits have been organised for researchers and research support staff, in areas such as Good Clinical Practice and Good Clinical Laboratory Practice, bioinformatics, ISO accreditation and research ethics. Notably, one of the network’s sites has created an internal monitoring unit, to establish a systematic process for clinical study monitoring. Successful applications were made for two EDCTP senior fellowships and one preparatory fellowship under the TESA II umbrella.

Members of the network have been successful in attracting grants from EDCTP and elsewhere, including the PreFit study, which is evaluating possible predictors of active TB disease, the ADAM project, exploring use of mass drug administration in malaria elimination, and the MAMAH project, evaluating malaria treatment in pregnant women receiving antiretroviral drugs. TESA partners were also collaborating on the XACTIII TB mobile case-finding study, the ERASE-TB household contact screening study, the TriageTB study, which is evaluating point-of-care triaging tools for TB, and Stool4TB study, which is testing the use of stool samples for TB diagnosis in children and people living with HIV.

In the TESA III grant, the network aims to continue this successful model to build the capacity of less well-developed sites. The three reference sites will act as key centres of technical excellence, hosting short- and long-term training stays. The EDCTP-funded projects will offer opportunities for hands-on training in multiple aspects of clinical research and capacity building in laboratory skills.

The network has expanded further to include eSwatini. It also plans to strengthen its links with policymakers and other regional stakeholders. Events are being organised to strengthen relationships with policymakers and support greater evidence-informed decision-making.

In 2021, TESA II won a grant from UK DHSC to support a fellowship program that would support up to eight female PhD candidates selected from TESA partners. The program titled “TESA addressing gender and diversity regional gaps in clinical research capacity” (TAGENDI) is aimed at reducing the gender and diversity gaps in the Southern Region through training of female TESA network researchers.

Impact

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

TESA III is drawing on existing centres of excellence in Southern Africa, links to European institutions, and ongoing clinical studies to build clinical and laboratory research capacities in less well-developed research centres. It is also strengthening collaborations with other networks with similar aims and with policymakers to coordinate activities and achieve greater impact.